Motion-robust super-resolution diffusion weighted MRI of early brain development The overall objective of this research is to dramatically improve technology and knowledge for in-vivo analysis of normal and abnormal white matter structure and neural connectivity before and early after birth when the brain undergoes its most rapid formative growth. Diffusion-weighted magnetic resonance imaging (DW-MRI or DWI) is considered one of the most promising tools for in-vivo analysis of neural structure; however, our ability to image the fetal and neonatal brain with this technique is constrained by several limitations; including subject motion, limited spatial resolution, and geometric distortion. There s a critical need for motion-robust high- resolution DWI imaging of fetuses and neonates. Due to the lack of such imaging technology, our understanding of early brain growth and the most commonly seen neurodevelopmental abnormalities is largely limited to insights from postmortem (in-vitro) studies. This project aims to fill these gaps through the development of an innovative, motion-robust, super-resolution, C. This involves the development and evaluation of a novel approach, built upon the physics of MRI and advanced image processing techniques, which corrects motion and reconstructs high-resolution DWI data to delineate the neural microstructure of the small fetal and neonatal brain. The two specific aims of this project target 1) moving subjects (aiming at improving neonatal DWI), and 2) fetuses, respectively; and aim at achieving high- resolution fractional anisotropy maps as well as single tensor and multi-tensor models of the neural fiber bundles in the developing brain despite subject movements. This contribution is important because it 1) enables in-vivo high-resolution mapping of the neural connectivity in fetal brain despite intermittent fetal and maternal motion, 2) significantly simpliies research MRI of neonates and preterm infants through a motion- robust imaging protocol that compensates for small head movements, 3) reduces the need for sedation and anesthesia in clinical MRI of neonates and non-cooperative patients, and 4) simultaneously corrects for motion and increases the spatial resolution of DWI, thus leads to dramatic improvements in the analysis of neural structure and connectivity in early brain development. Because the brain is incapable of self-repair and regeneration, interventions at early stages of brain growth are crucial. The development of neural rescue interventions, such as brain hypothermia, an intervention that has been shown to reduce brain damage due to birth asphyxia, is highly dependent upon accurate in-vivo analysis. Likewise, the evaluation of disruption or delay in neural development (due to premature birth or congenital anomalies) relies heavily on precise in-vivo analysis. The in-vivo analysis of early brain development proposed under this application is crucial to executing these research objectives.